Confusion is not the outcome any woman wants when presented with the results of genetic testing meant to assess her risk of cancer. But although it's becoming easier to identify the presence of cancer-associated mutations, it's still very difficult to translate those mutations into an estimate of future cancer risk in a way that is helpful to women and their clinicians.

Now Stanford cancer geneticist Allison Kurian, MD, and cancer specialist Michael Hall, MD, from Fox Chase Cancer Center in Philadelphia looked at the genetic test results for nearly 100,000 women who chose to be tested for the presence of mutations associated with the development of breast or ovarian cancer. They published their findings in JCO Precision Oncology.

Increasingly, women who are tested for a panel of cancer-associated mutations are given a mixed bag of results. Advances in DNA sequencing have made it quicker, easier and cheaper to identify mutations in an ever-growing panel of cancer-associated genes. With the exception of a few well-studied mutations such as BRCA1 and BRCA2, however, the exact effect of most of these remains murky because few large-scale studies have been completed.

The researchers assessed the mutation status of 95,561 women with and without the disease who chose to have their genome tested by Myriad Genetics for the presence of 25 cancer-associated mutations between September 2013 and September 2016. They matched the women according to their ages, ethnicity and family history of cancer to assign a relative risk of developing cancer to each of the mutations.

The researchers found that many of their results paralleled those of smaller studies, but there were some surprises. One mutation assumed to increase a woman’s risk of breast cancer was shown to instead increase the likelihood of ovarian cancer, while other mutations thought to increase the risk of breast cancer seemed instead to have little effect.

From our release:

The researchers hope the study is the first step to providing much-needed clarity to women and their physicians as they struggle to interpret the results of genetic testing. It may also help guideline-making organizations such as the American Cancer Society recommend when additional or more-frequent screening tests might be appropriate.

The scenario many of us learned in school is that two X chromosomes make someone female, and an X and a Y chromosome make someone male. These are simplistic ways of thinking about what is scientifically very complex.